OXA-48 carbapenem-hydrolyzing class D β-lactamase (OXA-48)

OXA-48 carbapenem-hydrolyzing class D β-lactamase is a significant enzyme produced by Gram-negative bacteria that confers resistance to carbapenem antibiotics, which are often used as last-line treatments for serious infections (Pitout et al., 2019, Clinical Microbiology Reviews). First identified in Klebsiella pneumoniae, this enzyme has spread globally due to its location on highly mobile plasmids, facilitating rapid horizontal gene transfer (Poirel et al., 2012, Emerging Infectious Diseases). Unlike many other carbapenemases, OXA-48 specifically hydrolyzes penicillins and carbapenems but has minimal activity against expanded-spectrum cephalosporins, making it difficult to detect through standard clinical screening (Evans & Amyes, 2014, Clinical Microbiology Reviews). The enzyme operates as a serine-hydrolase, utilizing a catalytic serine residue to open the β-lactam ring of the antibiotic, thereby neutralizing its bactericidal effect. Therapeutic management of OXA-48-producing organisms typically involves the use of novel β-lactamase inhibitors, such as avibactam, which covalently bind to the enzyme's active site to restore the efficacy of partner antibiotics like ceftazidime (Lahiri et al., 2013, Antimicrobial Agents and Chemotherapy). The emergence of OXA-48 variants and their co-occurrence with other resistance mechanisms, such as metallo-β-lactamases, poses a severe challenge to modern medicine and infection control. Consequently, OXA-48 is a primary target for the development of next-generation antimicrobial agents designed to overcome increasingly complex bacterial resistance profiles.

Other names

OXA-48-like carbapenemaseClass D β-lactamaseCarbapenem-hydrolyzing oxacillinase-48blaOXA-48

Inhibition of the enzyme's active-site serine residue through covalent or non-covalent binding, thereby preventing the hydrolysis of β-lactam antibiotics and restoring their antibacterial activity (Drawz & Bonomo, 2010, Clinical Microbiology Reviews).